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目的研究高脂血症所致大鼠急性胰腺炎早期基因表达变化。方法以高脂饮食(77%普通饲料+20%猪油+3%胆固醇)制备高脂血症SD大鼠模型,取正常和高脂大鼠各18只,铃蟾肽腹腔注射制备急性水肿型胰腺炎(AEP),两组其余各38只动物逆行胰胆管注射牛磺胆酸钠制备急性坏死型胰腺炎(ANP)。观察各组大鼠3、6、24 h胰腺组织病理学变化差异(每组6只),并比较1周时两组ANP大鼠的死亡率(每组20只)。采用高密度寡核苷酸芯片观察急性胰腺炎早期胰腺基因表达谱变化。结果1周时高脂ANP组死亡率明显高于单纯ANP组(75%比50%);参照Schmidt胰腺组织半定量积分法,高脂各组较相对应正常血脂组的胰腺坏死、出血、炎性细胞浸润程度均加重,尤以6 h组为最。6 h时,高脂AEP组与正常血脂AEP组相比,水肿、坏死、出血、炎性细胞浸润指数分别为:3.92±0.20比3.00±0.00、3.92±0.20比2.42±0.49、1.83±0.26比0.42±0.20、1.83±0.26比0.58±0.38,差异有统计学意义(P值均<0.05)。高脂ANP与正常血脂ANP组相比,坏死、出血、炎性细胞浸润指数分别为:4.00±0.00比3.25±0.29、3.42±0.80比1.80±1.09、2.67±1.03比1.13±0.25,差异有统计学意义(P值均<0.05);水肿指数为3.58±0.38比3.25±0.29,差异无统计学意义(P>0.05)。急性胰腺炎诱导3 h后,高脂组及正常血脂组胰腺表达均上调的基因有10个,表达均下调的基因有49个(其中11个为表达序列标签,EST)。结论高脂血症可增加大鼠ANP时的死亡率,加重大鼠AEP和ANP时胰腺病理变化;其机制可能为高脂血症影响信号转导,加重氧化应激、能量代谢紊乱等。
Objective To study the early gene expression of acute pancreatitis induced by hyperlipidemia in rats. Methods Hyperlipidemia SD rat model was induced by high fat diet (77% normal diet + 20% lard + 3% cholesterol). 18 normal and hyperlipidemic rats were injected with bombesin to prepare acute edema Acute pancreatitis (AEP) was induced by injection of sodium taurocholate into the remaining 38 animals in each group. The pathological changes of pancreas were observed at 3, 6 and 24 h in each group (6 rats in each group). The mortality of ANP rats in each group was compared at 1 week (20 rats in each group). High-density oligonucleotide microarray was used to observe the changes of pancreatic gene expression in early stage of acute pancreatitis. Results The mortality of the high-fat ANP group was significantly higher than that of the pure ANP group (75% vs 50%) at 1 week. According to Schmidt’s semi-quantitative integration method, the hyperlipidemic pancreatic necrosis, hemorrhage and inflammation The degree of infiltration of cells were aggravated, especially in the 6 h group. At 6 h, the indexes of edema, necrosis, hemorrhage and inflammatory cell infiltration in high-fat AEP group were 3.92 ± 0.20 compared with 3.00 ± 0.00, 3.92 ± 0.20, 2.42 ± 0.49 and 1.83 ± 0.26 respectively 0.42 ± 0.20, 1.83 ± 0.26 and 0.58 ± 0.38, respectively (all P <0.05). The indexes of necrosis, hemorrhage and inflammatory cell infiltration in hyperlipemic ANP group were 4.00 ± 0.00, 3.25 ± 0.29, 3.42 ± 0.80, 1.80 ± 1.09, 2.67 ± 1.03, 1.13 ± 0.25, respectively (P <0.05). The edema index was 3.58 ± 0.38 vs 3.25 ± 0.29, with no significant difference (P> 0.05). After 3 h of induction of acute pancreatitis, there were 10 genes that were upregulated in the pancreas of hyperlipidemic and normal lipids groups, and 49 of them were down-regulated (11 of them were ESTs). Conclusion Hyperlipidemia may increase the ANP mortality and aggravate the pathological changes of pancreas in rats with AEP and ANP. The possible mechanism is that hyperlipidemia affects signal transduction, aggravates oxidative stress and energy metabolism disorders.